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Programmable probiotics modulate inflammation and gut microbiota for inflammatory bowel disease treatment after effective oral delivery

Author

Listed:
  • Jun Zhou

    (Soochow University)

  • Maoyi Li

    (Soochow University)

  • Qiufang Chen

    (Anhui Medical University)

  • Xinjie Li

    (Soochow University)

  • Linfu Chen

    (Soochow University)

  • Ziliang Dong

    (Soochow University)

  • Wenjun Zhu

    (Soochow University)

  • Yang Yang

    (Tongji University School of Medicine)

  • Zhuang Liu

    (Soochow University)

  • Qian Chen

    (Soochow University)

Abstract

Reactive oxygen species (ROS) play vital roles in intestinal inflammation. Therefore, eliminating ROS in the inflammatory site by antioxidant enzymes such as catalase and superoxide dismutase may effectively curb inflammatory bowel disease (IBD). Here, Escherichia coli Nissle 1917 (ECN), a kind of oral probiotic, was genetically engineered to overexpress catalase and superoxide dismutase (ECN-pE) for the treatment of intestinal inflammation. To improve the bioavailability of ECN-pE in the gastrointestinal tract, chitosan and sodium alginate, effective biofilms, were used to coat ECN-pE via a layer-by-layer electrostatic self-assembly strategy. In a mouse IBD model induced by different chemical drugs, chitosan/sodium alginate coating ECN-pE (ECN-pE(C/A)2) effectively relieved inflammation and repaired epithelial barriers in the colon. Unexpectedly, such engineered EcN-pE(C/A)2 could also regulate the intestinal microbial communities and improve the abundance of Lachnospiraceae_NK4A136 and Odoribacter in the intestinal flora, which are important microbes to maintain intestinal homeostasis. Thus, this study lays a foundation for the development of living therapeutic proteins using probiotics to treat intestinal-related diseases.

Suggested Citation

  • Jun Zhou & Maoyi Li & Qiufang Chen & Xinjie Li & Linfu Chen & Ziliang Dong & Wenjun Zhu & Yang Yang & Zhuang Liu & Qian Chen, 2022. "Programmable probiotics modulate inflammation and gut microbiota for inflammatory bowel disease treatment after effective oral delivery," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31171-0
    DOI: 10.1038/s41467-022-31171-0
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    References listed on IDEAS

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    1. Zhenping Cao & Xinyue Wang & Yan Pang & Shanshan Cheng & Jinyao Liu, 2019. "Biointerfacial self-assembly generates lipid membrane coated bacteria for enhanced oral delivery and treatment," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    2. Daniel S. Leventhal & Anna Sokolovska & Ning Li & Christopher Plescia & Starsha A. Kolodziej & Carey W. Gallant & Rudy Christmas & Jian-Rong Gao & Michael J. James & Andres Abin-Fuentes & Munira Momin, 2020. "Immunotherapy with engineered bacteria by targeting the STING pathway for anti-tumor immunity," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    3. Raymond W. Bourdeau & Audrey Lee-Gosselin & Anupama Lakshmanan & Arash Farhadi & Sripriya Ravindra Kumar & Suchita P. Nety & Mikhail G. Shapiro, 2018. "Acoustic reporter genes for noninvasive imaging of microorganisms in mammalian hosts," Nature, Nature, vol. 553(7686), pages 86-90, January.
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